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Inflammatory macrophage derived TNFα downregulates estrogen receptor α via FOXO3a inactivation in human breast cancer cells
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- Gunnarsdóttir, Frida Björk (author)
- Lund University,Lunds universitet,Cancerimmunologi, Malmö,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Cancer Immunology, Malmö,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Hagerling, Catharina (author)
- Lund University,Lunds universitet,Cancerimmunologi, Malmö,Forskargrupper vid Lunds universitet,Cancercellers evolution,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Cancer Immunology, Malmö,Lund University Research Groups,Pathways of cancer cell evolution,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Bergenfelz, Caroline (author)
- Lund University,Lunds universitet,Cancerimmunologi, Malmö,Forskargrupper vid Lunds universitet,Cancer Immunology, Malmö,Lund University Research Groups
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- (creator_code:org_t)
- Elsevier BV, 2020
- 2020
- English.
- In: Experimental Cell Research. - : Elsevier BV. - 0014-4827. ; 390:1
- Journal article (peer-reviewed)
Abstract
Subject headings
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- Patients with estrogen receptor α positive (ERα+) breast cancer can respond to endocrine therapy, but treatment resistance is common and associated with downregulation of ERα expression in the dormant residual cells. Here we show, using long-term NSG xenograft models of human breast cancer and primary human monocytes, in vitro primary cell cultures and tumors from breast cancer patients, that macrophage derived tumor necrosis factor alpha (TNFα) downregulates ERα in breast cancer cells via inactivation of the transcription factor Forkhead box O transcription factor 3a (FOXO3a). Moreover, presence of tumor associated macrophages in the primary tumor of breast cancer patients, was associated with ERα negativity, and with worse prognosis in patients with ERα+ tumors. We propose that pro-inflammatory macrophages, despite being tumoricidal, may have direct effects on tumor progression and endocrine resistance in breast cancer patients. Our findings suggest that TNFα antagonists should be evaluated for treatment of ERα+ breast cancer.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Breast cancer
- Endocrine resistance
- Estrogen receptor
- FOXO3a
- Macrophage
- TNFalpha
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- art (subject category)
- ref (subject category)
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